Characteristics of L-Citrulline Transport across Rat Small Intestine In Vitro

Vadgama, Jaydutt V.; Evered, David

doi:10.1203/00006450-199210000-00019

Cited by 36 publications

(28 citation statements)

References 28 publications

(31 reference statements)

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“…At the brush border L-citrulline shares the Na + -dependent active transport system for neutral aminoacids that has been previously described for the mucosal brush border membranes of the rabbit jejunum (88). L-citrulline can also be transported by a system analogous to system ASC described for nonepithelial cells and for basolateral membranes of certain epithelia (88).…”

Section: L-citrulline Transport Intestinementioning

confidence: 75%

Therapeutic Use of Citrulline in Cardiovascular Disease

Romero

Platt

Caldwell

2006

Cardiovascular Drug Reviews

190

178

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L-citrulline is the natural precursor of L-arginine, substrate for nitric oxide synthase (NOS) in the production of NO. Supplemental administration L-arginine has been shown to be effective in improving NO production and cardiovascular function in cardiovascular diseases associated with endothelial dysfunction, such as hypertension, heart failure, atherosclerosis, diabetic vascular disease and ischemia-reperfusion injury, but the beneficial actions do not endure with chronic therapy. Substantial intestinal and hepatic metabolism of L-arginine to ornithine and urea by arginase makes oral delivery very ineffective. Additionally, all of these disease states as well as supplemental L-arginine enhance arginase expression and activity, thus reducing the effectiveness of L-arginine therapy. In contrast, L-citrulline is not metabolized in the intestine or liver and does not induce tissue arginase, but rather inhibits its activity. L-citrulline entering the kidney, vascular endothelium and other tissues can be readily converted to L-arginine, thus raising plasma and tissue levels of L-arginine and enhancing NO production. Supplemental L-citrulline has promise as a therapeutic adjunct in disease states associated with L-arginine deficiencies.

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Section: L-citrulline Transport Intestinementioning

confidence: 75%

Therapeutic Use of Citrulline in Cardiovascular Disease

Romero

Platt

Caldwell

2006

Cardiovascular Drug Reviews

190

178

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“…Citrulline uptake by the kidney always exceeded the filtered load by nearly 30%, signifying that some transport of citrulline occurs beyond the glomerulus (possibly the basolateral aspect of proximal tubule epithelia) and that GFR alone might not dictate citrulline availability. In support of this, Gekle and Silbernagl (5,6) describe basolateral citrulline transport in the everted toad bladder, a longstanding model of renal tubule epithelia and that a carrier-mediated citrulline transporter has been characterized in epithelia of the rat gut (27). The fact that citrulline is taken up from postglomerular plasma may help explain how the nonfiltering kidney could persist as a net producer of arginine, something that is of interest in the clinical setting of acute and chronic renal failure.…”

Section: Discussionmentioning

confidence: 88%

Production of arginine by the kidney is impaired in a model of sepsis: early events following LPS

Lortie¹,

Satriano²,

Gabbai³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Lipopolysaccharide (LPS) is used experimentally to elicit the innate physiological responses observed in human sepsis. We have previously shown that LPS causes depletion of plasma arginine before inducible nitric oxide synthase (iNOS) activity, indicating that changes in arginine uptake and/or production rather than enhanced consumption are responsible. Because the kidney is the primary source of circulating arginine and renal failure is a hallmark of septicemia, we determined the time course of changes in arginine metabolism and kidney function relative to iNOS expression. LPS given intravenously to anesthetized rats caused a decrease in mean arterial blood pressure after 120 min that coincided with increased plasma nitric oxide end products (NOx) and iNOS expression in lung and liver. Interestingly, impairment of renal function preceded iNOS activity by 30-60 min and occurred in tandem with decreased renal arginine production. The baseline rate of renal arginine production was approximately 60 micromol.h(-1).kg(-1), corresponding to an apparent plasma half-life of approximately 20 min, and decreased by one-half within 60 min of LPS. Calculations based on the systemic production and clearance show that normally only 5% of kidney arginine output is destined to become nitric oxide and that <25% of LPS-impaired renal production was converted to NOx in the first 4 h. In addition, we provide novel observations indicating that the kidney appears refractory to iNOS induction by LPS because no discernible enhancement of renal NOx production occurred within 4 h, and iNOS expression in the kidney was muted compared with that in liver or lung. These studies demonstrate that the major factor responsible for the rapid decrease in extracellular arginine content following LPS is impaired production by the kidney, a phenomenon that appears linked to reduced renal perfusion.

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“…Transplacental transport of citrulline is not well characterized. In the rat small intestine and the apical membrane of renal proximal tubular cells, citrulline transport appears to occur via Na + -dependent systems [40, 41]. IUGR is associated with elevated levels of maternal arginine [42], but intracellular arginine and citrulline are reduced in human umbilical vein cells (HUVECs) [39].…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons

Pantham

Rosario

Weintraub

et al. 2016

Biology of Reproduction

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Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR. We hypothesized that placental amino acid transport capacity is reduced prior to onset of reduced fetal growth in baboons with maternal nutrient restriction (MNR). Pregnant baboons were fed either a control (n ¼ 8) or MNR diet (70% of control diet, n ¼ 9) from Gestational Day 30. At Gestational Day 120 (0.65 of gestation), fetuses and placentas were collected. Microvillous (MVM) and basal (BM) plasma membrane vesicles were isolated. System A and system L transport activity was determined in MVM, and leucine transporter activity was assessed in BM using radiolabeled substrates. MVM amino acid transporter isoform expression (SNAT1, SNAT2, and SNAT4 and LAT1 and LAT2) was measured using Western blots. LAT1 and LAT2 expression were also determined in BM. Maternal and fetal plasma amino acids concentrations were determined using mass spectrometry. Fetal and placental weights were unaffected by MNR. MVM system A activity was decreased by 37% in MNR baboon placentas (P ¼ 0.03); however MVM system A amino acid transporter protein expression was unchanged. MVM system L activity and BM leucine transporter activity were not altered by MNR. Fetal plasma concentrations of essential amino acids isoleucine and leucine were reduced, while citrulline increased (P , 0.05) in MNR fetuses compared to controls. In this primate model of IUGR, placental MVM system A amino acid transporter activity is decreased prior to the onset of reduction in the fetal growth trajectory. The reduction in plasma leucine and isoleucine in MNR fetuses may be caused by reduced activity of MVM system A, which is strongly coupled with system L essential amino acid uptake. Our findings indicate that reduced placental amino acid transport may be a cause rather than a consequence of IUGR due to inadequate maternal nutrition.

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Characteristics of L-Citrulline Transport across Rat Small Intestine In Vitro

Cited by 36 publications

References 28 publications

Therapeutic Use of Citrulline in Cardiovascular Disease

Therapeutic Use of Citrulline in Cardiovascular Disease

Production of arginine by the kidney is impaired in a model of sepsis: early events following LPS

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons

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